title: The role of dendritic spine morphology in the compartmentalization and delivery of surface receptors.
abstract: Since AMPA receptors are major molecular players in both short- and long-term plasticity, it is important to identify the time-scales of and factors affecting the lateral diffusion of AMPARs on the dendrite surface. Using a mathematical model, we study how the dendritic spine morphology affects two processes: (1) compartmentalization of the surface receptors in a single spine to retain local chemistry and (2) the delivery of receptors to the post-synaptic density (PSD) of spines via lateral diffusion following insertion onto the dendrite shaft. Computing the mean first passage time (MFPT) of surface receptors on a sample of real spine morphologies revealed that a constricted neck and bulbous head serve to compartmentalize receptors, consistent with previous works. The residence time of a Brownian diffusing receptor on the membrane of a single spine was computed to be ∼ 5 s. We found that the location of the PSD corresponds to the location at which the maximum MFPT occurs, the position that maximizes the residence time of a diffusing receptor. Meanwhile, the same geometric features of the spine that compartmentalize receptors inhibit the recruitment of AMPARs via lateral diffusion from dendrite insertion sites. Spines with narrow necks will trap a smaller fraction of diffusing receptors in the their PSD when considering competition for receptors between the spines, suggesting that ideal geometrical features involve a tradeoff depending on the intent of compartmentalizing the current receptor pool or recruiting new AMPARs in the PSD. The ultimate distribution of receptors among the spine PSDs by lateral diffusion from the dendrite shaft is an interplay between the insertion location and the shape and locations of both the spines and their PSDs. The time-scale for delivery of receptors to the PSD of spines via lateral diffusion was computed to be ∼ 60 s.
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of California, Berkeley, CA, USA, corymsimon@gmail.com.
authors.forename: Cory M
authors.initials: CM
authors.lastname: Simon
authors.forename: Iain
authors.initials: I
authors.lastname: Hepburn
authors.forename: Weiliang
authors.initials: W
authors.lastname: Chen
authors.forename: Erik
authors.initials: E
authors.lastname: De Schutter
mesh_terms: D048430:Cell Shape / Q000502:physiology; D049229:Dendritic Spines / Q000378:metabolism*; D006801:Humans; D008959:Models, Neurological; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D021381:Protein Transport; D018091:Receptors, AMPA / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*
chemical_list: D018091:Receptors, AMPA; D011956:Receptors, Cell Surface